tbuckley/cabot-search huggingface dataset:
Applications of injectable hemostatic materials in wound healing: principles, strategies, performance requirements, and future perspectives
Authors: Hong Wang, Liang Yang
Journal: Theranostics (2023)

Uncontrolled traumatic bleeding can lead to death due to excessive blood loss within minutes.Early intervention is crucial to save lives, making timely and effective hemostasis is a major global challenge.Injectable hemostatic materials (IHMs) have been proposed to improve the effectiveness of hemostasis, facilitate wound healing, and enhance survival rates in emergency situations.The superior hemostatic performance of IHMs has garnered significant attention.However, there are relatively few comprehensive reviews on IHMs.This paper aims to provide a comprehensive review of the latest research progress on IHMs in recent years.Firstly, the physiological hemostatic process and the underlying principles of hemostasis are analyzed.Subsequently, the synthesis strategies for different IHMs are discussed.The performance requirements of IHMs are then summarized, including high efficiency, biocompatibility, degradability, manipulability, stability and antibacterial ability.Finally, the development prospects and challenges of IHMs are presented.This review serves as a necessary and systematic summary of IHMs, providing a valuable reference for the development of new high-performance hemostatic materials and their practical clinical applications.
Three-dimensional nanofibrous sponges with aligned architecture and controlled hierarchy regulate neural stem cell fate for spinal cord regeneration
Authors: Zhiwei Li, Ye Qi, Lei Sun, Zheng Li, Shaojuan Chen, Yuqi Zhang, Yuan Ma, Jinming Han, Zide Wang, Yulin Zhang, Huimin Geng, Bin Huang, Jian Wang, Gang Li, Xingang Li, Shaohua Wu, Shilei Ni
Journal: Theranostics (2023)

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to severe neurological dysfunction and even permanent paralysis.A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for SCI treatment.Methods: Innovative three-dimensional (3D) nanofibrous sponges (NSs) were designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment.Immunofluorescence, mRNA sequencing, magnetic resonance imaging, electrophysiological analysis, and behavioral tests were used to investigate the in vitro and in vivo regenerative effects of the 3D NSs.Results: The generated 3D NSs exhibited uniaxially aligned nano-architecture and highly controllable hierarchical structure with super-high porosity (99%), outstanding hydrophilicity, and reasonable mechanical performance.They facilitated cell infiltration, induced cell alignment, promoted neuronal differentiation of NSCs, and enhanced their maturation mediated through cellular adhesion molecule pathways.In vivo, the NSC-seeded 3D NSs efficiently promoted axon reinnervation and remyelination in a rat SCI model, with new "neural relays" developing across the lesion gap.These histological changes were associated with regain of function, including increasing the neurological motor scores of SCI rats, from approximately 2 to 16 (out of 21), and decreasing the sensing time in the tape test from 140 s to 36 s.Additionally, the scaffolds led to restoration of ascending and descending electrophysiological signalling. Conclusion:The as-fabricated 3D NSs effectively regulate NSC fates, and an advanced combination of 3D NS design and transplanted NSCs enables their use as an ideal tissue-engineered scaffold for SCI repair.
5-aminolevulinate and CHIL3/CHI3L1 treatment amid ischemia aids liver metabolism and reduces ischemia-reperfusion injury
Authors: Guanghui Jin, Na Guo, Yasong Liu, Lele Zhang, Liang Chen, Tao Dong, Wei Liu, Xiaomei Zhang, Yong Jiang, Guo Lv, Fei Zhao, Wei Liu, Ziqing Hei, Yang Yang, Jingxing Ou
Journal: Theranostics (2023)

Rationale: Liver resection and transplantation surgeries are accompanied by hepatic ischemia-reperfusion (HIR) injury that hampers the subsequent liver recovery. Given that the liver is the main organ for metabolism and detoxification, ischemia-reperfusion in essence bestows metabolic stress upon the liver and disrupts local metabolic and immune homeostasis. Most of the recent and current research works concerning HIR have been focusing on addressing HIR-induced hepatic injury and inflammation, instead of dealing with the metabolic reprogramming and restoration of redox homeostasis. As our previous work uncovers the importance of 5-aminolevulinate (5-ALA) synthesis during stress adaptation, here we evaluate the effects of supplementing 5-ALA to mitigate HIR injury. Methods: 5-ALA was supplemented into the mice or cultured cells during the ischemic or oxygen-glucose deprivation (OGD) phase. Following reperfusion or reoxygenation, cellular metabolism and energy homeostasis, mitochondrial production of reactive oxygen species (ROS) and transcriptomic changes were evaluated in HIR mouse models or cultured hepatocytes and macrophages. Liver injury, hepatocytic functional tests, and macrophagic M1/M2 polarization were assessed. Results: Dynamic changes in the expression of key enzymes in 5-ALA metabolism were first confirmed in donor and mouse liver samples following HIR. Supplemented 5-ALA modulated mouse hepatic lipid metabolism and reduced ATP production in macrophages following HIR, resulting in elevation of anti-inflammatory M2 polarization. Mechanistically, 5-ALA down-regulates macrophagic chemokine receptor CX3CR1 via the repression of RelA following OGD and reoxygenation (OGD/R). Cx3cr1 KO mice demonstrated milder liver injuries and more macrophage M2 polarization after HIR. M2 macrophage-secreted chitinase-like protein 3 (CHIL3; CHI3L1 in human) is an important HIR-induced effector downstream of CX3CR1 deficiency. Addition of CHIL3/CHI3L1 alone improved hepatocellular metabolism and reduced OGD/R-inflicted injuries in cultured mouse and human hepatocytes. Combined treatment with 5-ALA and CHIL3 during the ischemic phase facilitated lipid metabolism and ATP production in the mouse liver following HIR. Conclusion: Our results reveal that supplementing 5-ALA promotes macrophagic M2 polarization via downregulation of RelA and CX3CR1 in mice following HIR, while M2 macrophage-produced CHIL3/CHI3L1 also manifests beneficial effects to the recovery of hepatic metabolism. 5-ALA and CHIL3/CHI3L1 together mitigate HIR-induced mitochondrial dysfunction and hepatocellular injuries, which may be developed into safe and effective clinical treatments to attenuate HIR injuries.
The effects of pathogenic and likely pathogenic variants for inherited hemostasis disorders in 140 214 UK Biobank participants
Authors: Luca Stefanucci, Janine Collins, Matthew C. Sims, Inigo Barrio-Hernandez, Luanluan Sun, Oliver S. Burren, Livia Perfetto, Isobel Bender, Tiffany J. Callahan, Kathryn Fleming, Jose A. Guerrero, Henning Hermjakob, Maria J. Martin, James Stephenson, Kalpana Paneerselvam, Slavé Petrovski, Pablo Porras, Peter N. Robinson, Quanli Wang, Xavier Watkins, Mattia Frontini, Roman A. Laskowski, Pedro Beltrao, Emanuele Di Angelantonio, Keith Gomez, Mike Laffan, Willem H. Ouwehand, Andrew D. Mumford, Kathleen Freson, Keren Carss, Kate Downes, Nick Gleadall, Karyn Megy, Elspeth Bruford, Dragana Vuckovic
Journal: Blood (2023)

Abstract Rare genetic diseases affect millions, and identifying causal DNA variants is essential for patient care. Therefore, it is imperative to estimate the effect of each independent variant and improve their pathogenicity classification. Our study of 140 214 unrelated UK Biobank (UKB) participants found that each of them carries a median of 7 variants previously reported as pathogenic or likely pathogenic. We focused on 967 diagnostic-grade gene (DGG) variants for rare bleeding, thrombotic, and platelet disorders (BTPDs) observed in 12 367 UKB participants. By association analysis, for a subset of these variants, we estimated effect sizes for platelet count and volume, and odds ratios for bleeding and thrombosis. Variants causal of some autosomal recessive platelet disorders revealed phenotypic consequences in carriers. Loss-of-function variants in MPL, which cause chronic amegakaryocytic thrombocytopenia if biallelic, were unexpectedly associated with increased platelet counts in carriers. We also demonstrated that common variants identified by genome-wide association studies (GWAS) for platelet count or thrombosis risk may influence the penetrance of rare variants in BTPD DGGs on their associated hemostasis disorders. Network-propagation analysis applied to an interactome of 18 410 nodes and 571 917 edges showed that GWAS variants with large effect sizes are enriched in DGGs and their first-order interactors. Finally, we illustrate the modifying effect of polygenic scores for platelet count and thrombosis risk on disease severity in participants carrying rare variants in TUBB1 or PROC and PROS1, respectively. Our findings demonstrate the power of association analyses using large population datasets in improving pathogenicity classifications of rare variants.
Molecular MRD is strongly prognostic in patients with <i>NPM1</i>-mutated AML receiving venetoclax-based nonintensive therapy
Authors: Jad Othman, Ing S. Tiong, Jenny O'Nions, Mike Dennis, Katya Mokretar, Adam Ivey, Michael Austin, Anne-Louise Latif, Mariam Amer, Wei Yee Chan, Charles Crawley, Francesca Crolla, Joe Cross, Ray Dang, Johnathon Elliot, Chun Y. Fong, Sofia Galli, Paolo Gallipoli, Francesca Hogan, Pallavi Kalkur, Anjum Khan, Pramila Krishnamurthy, John Laurie, Sun Loo, Scott Marshall, Priyanka Mehta, Vidhya Murthy, Sateesh Nagumantry, Srinivas Pillai, Nicola Potter, Rob Sellar, Tom Taylor, Rui Zhao, Nigel H. Russell, Andrew H. Wei, Richard Dillon
Journal: Blood (2023)

Assessment of measurable residual disease (MRD) by quantitative reverse transcription polymerase chain reaction is strongly prognostic in patients with NPM1-mutated acute myeloid leukemia (AML) treated with intensive chemotherapy; however, there are no data regarding its utility in venetoclax-based nonintensive therapy, despite high efficacy in this genotype. We analyzed the prognostic impact of NPM1 MRD in an international real-world cohort of 76 previously untreated patients with NPM1-mutated AML who achieved complete remission (CR)/CR with incomplete hematological recovery following treatment with venetoclax and hypomethylating agents (HMAs) or low-dose cytarabine (LDAC). A total of 44 patients (58%) achieved bone marrow (BM) MRD negativity, and a further 14 (18%) achieved a reduction of ≥4 log10 from baseline as their best response, with no difference between HMAs and LDAC. The cumulative rates of BM MRD negativity by the end of cycles 2, 4, and 6 were 25%, 47%, and 50%, respectively. Patients achieving BM MRD negativity by the end of cycle 4 had 2-year overall of 84% compared with 46% if MRD was positive. On multivariable analyses, MRD negativity was the strongest prognostic factor. A total of 22 patients electively stopped therapy in BM MRD-negative remission after a median of 8 cycles, with 2-year treatment-free remission of 88%. In patients with NPM1-mutated AML attaining remission with venetoclax combination therapies, NPM1 MRD provides valuable prognostic information.
A phase 2 trial of CD24Fc for prevention of graft-versus-host disease
Authors: John Magenau, Samantha Jaglowski, Joseph Uberti, Sherif S. Farag, Mary Mansour Riwes, Attaphol Pawarode, Sarah Anand, Monalisa Ghosh, John Maciejewski, Thomas Braun, Martin Devenport, Susan Lu, Bhramori Banerjee, Carolyn DaSilva, Steven Devine, Mei-Jie Zhang, Linda J. Burns, Yang Liu, Pan Zheng, Pavan Reddy
Journal: Blood (2023)
Towards precision medicine in migraine: Recent therapeutic advances and potential biomarkers to understand heterogeneity and treatment response
Authors: Gabriella Juhasz, Kinga Gecse, Daniel Baksa
Journal: Pharmacology & Therapeutics (2023)

After 35 years since the introduction of the International Classification of Headache Disorders (ICHD), we are living in the era of the second great revolution in migraine therapies. First, discoveries of triptans provided a breakthrough in acute migraine treatment utilizing bench-to-bedside research results on the role of serotonin in migraine. Next, the discovery of the role of neuropeptides, more specifically calcitonin gene-related peptide (CGRP) in migraine attack led to the development of anti-CGRP therapies that are effective both in acute and preventive treatment, and are also able to reduce migraine-related burden. Here, we reviewed the most recent clinical studies and real-world data on available migraine-specific medications, including triptans, ditants, gepants and anti-CGRP monoclonal antibodies. Novel drug targets, such as PACAP and amylins were also discussed. To address the main challenges of migraine therapy, the high heterogeneity of people with migraine, the prevalent presence of various comorbid disorders, and the insufficient medical care of migraine patients were covered. Promising novel approaches from the fields of omics, blood and saliva biomarker, imaging and provocation studies might bring solutions for these challenges with the potential to identify further drug targets, distinguish more homogeneous patient subgroups, contribute to more optimal drug selection strategies, and detect biomarkers in association with headache features or predicting treatment efficacy. In the future, the combined analysis of data of different biomarker modalities with machine learning algorithms may serve precision medicine in migraine treatment.
Author correction to “Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy” [Acta Pharm Sin B (2022) 4204–4223]
Authors: Zaigang Zhou, Jiashe Chen, Yu Liu, Chunjuan Zheng, Wenjuan Luo, Lele Chen, Shen Zhou, Zhiming Li, Jianliang Shen
Journal: Acta Pharmaceutica Sinica B (2023)

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].
Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin: Creation of an unnatural analogue with improved anticancer properties
Authors: Dexiu Yan, Jemma Arakelyan, Teng Wan, Ritvik Raina, Tsz Ki Chan, Dohyun Ahn, Vladimir Kushnarev, Tsz Kiu Cheung, Ho Ching Chan, Inseo Choi, Pui Yi Ho, Feijun Hu, Yujeong Kim, Hill Lam Lau, Ying Lo Law, Chi Seng Leung, Chun Yin Tong, Kai Kap Wong, Wing Lam Yim, Nikolay S. Karnaukhov, Richard Y.C. Kong, Maria V. Babak, Yudai Matsuda
Journal: Acta Pharmaceutica Sinica B (2023)

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin (1) and variecolactone (2) was identified in Aspergillus aculeatus ATCC 16872. Heterologous production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 VrcB. Intriguingly, the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues (5–7). Analysis of the compounds' anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities, 5 was associated with significantly reduced toxic side effects in cancer-bearing mice, indicating its potentially broader therapeutic window. Our study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.
Gut Microbiome in Patients With Early-Stage and Late-Stage Melanoma
Authors: Russell G. Witt, Samuel H. Cass, Tiffaney Tran, Ashish Damania, Emelie E. Nelson, Elizabeth Sirmans, Elizabeth M. Burton, Manoj Chelvanambi, Sarah Johnson, Hussein A. Tawbi, Jeffrey E. Gershenwald, Michael A. Davies, Christine Spencer, Aditya Mishra, Matthew C. Wong, Nadim J. Ajami, Christine B. Peterson, Carrie R. Daniel, Jennifer A. Wargo, Jennifer L. McQuade, Kelly C. Nelson
Journal: JAMA Dermatology (2023)

The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression.
Differences in Cholecystectomy Outcomes and Operating Time Between Male and Female Surgeons in Sweden
Authors: My Blohm, Gabriel Sandblom, Lars Enochsson, Johanna Österberg
Journal: JAMA Surgery (2023)

Importance Female surgeons are still in the minority worldwide, and highlighting gender differences in surgery is important in understanding and reducing inequities within the surgical specialty. Studies on different surgical procedures indicate equal results, or safer outcomes, for female surgeons, but it is still unclear whether surgical outcomes of gallstone surgery differ between female and male surgeons. Objective To examine the association of the surgeon’s gender with surgical outcomes and operating time in elective and acute care cholecystectomies. Design, Setting, and Participants A population-based cohort study based on data from the Swedish Registry of Gallstone Surgery was performed from January 1, 2006, to December 31, 2019. The sample included all registered patients undergoing cholecystectomy in Sweden during the study period. The follow-up time was 30 days. Data analysis was performed from September 1 to September 7, 2022, and updated March 24, 2023. Exposure The surgeon’s gender. Main Outcome(s) and Measure(s) The association between the surgeon’s gender and surgical outcomes for elective and acute care cholecystectomies was calculated with generalized estimating equations. Differences in operating time were calculated with mixed linear model analysis. Results A total of 150 509 patients, with 97 755 (64.9%) undergoing elective cholecystectomies and 52 754 (35.1%) undergoing acute care cholecystectomies, were operated on by 2553 surgeons, including 849 (33.3%) female surgeons and 1704 (67.7%) male surgeons. Female surgeons performed fewer cholecystectomies per year and were somewhat better represented at universities and private clinics. Patients operated on by male surgeons had more surgical complications (odds ratio [OR], 1.29; 95% CI, 1.19-1.40) and total complications (OR, 1.12; 95% CI, 1.06-1.19). Male surgeons had more bile duct injuries in elective surgery (OR, 1.69; 95% CI, 1.22-2.34), but no significant difference was apparent in acute care operations. Female surgeons had significantly longer operation times. Male surgeons converted to open surgery more often than female surgeons in acute care surgery (OR, 1.22; 95% CI, 1.04-1.43), and their patients had longer hospital stays (OR, 1.21; 95% CI, 1.11-1.31). No significant difference in 30-day mortality could be demonstrated. Conclusions and Relevance The results of this cohort study indicate that female surgeons have more favorable outcomes and operate more slowly than male surgeons in elective and acute care cholecystectomies. These findings may contribute to an increased understanding of gender differences within this surgical specialty.
Individual-level solutions may support system-level change â if they are internalized as part of one's social identity
Authors: Lina Koppel, Claire E. Robertson, Kimberly C. Doell, Ali M. Javeed, Jesper Rasmussen, Steve Rathje, Madalina Vlasceanu, Jay J. Van Bavel
Journal: Behavioral and Brain Sciences (2023)

Abstract System-level change is crucial for solving society's most pressing problems. However, individual-level interventions may be useful for creating behavioral change before system-level change is in place and for increasing necessary public support for system-level solutions. Participating in individual-level solutions may increase support for system-level solutions – especially if the individual-level solutions are internalized as part of one's social identity.
Elevated Risk of Visceral Malignant Neoplasms in Extramammary Paget Disease
Authors: Nolan J. Maloney, Hanqi Yao, Sumaira Z. Aasi, Esther M. John, Eleni Linos, Nour Kibbi
Journal: JAMA Dermatology (2023)

This cross-sectional study evaluates the incidence and types of cancers that develop years after an extramammary Paget disease (EMPD) diagnosis.
Genetic Variants, Serum 25-Hydroxyvitamin D Levels, and Sarcopenia
Authors: Tingting Sha, Yilun Wang, Yuqing Zhang, Nancy E. Lane, Changjun Li, Jie Wei, Chao Zeng, Guanghua Lei
Journal: JAMA Network Open (2023)

Vitamin D deficiency is commonly associated with sarcopenia; however, the latest International Clinical Practice Guidelines for Sarcopenia do not recommend vitamin D supplementation for sarcopenia owing to a lack of an apparent therapeutic effect on the indices of sarcopenia among participants with replete vitamin D concentration (ie, 25-hydroxyvitamin D [25(OH)D] level >20 ng/mL) from randomized clinical trials. While there is consensus in all vitamin D guidelines that serum levels of 25(OH)D less than 10 ng/mL should be corrected, approximately 30% of the world population's 25(OH)D levels range from 10 to 20 ng/mL, and it remains unclear whether such suboptimal levels can maintain optimal health, including sarcopenia risk.To investigate the association of serum 25(OH)D level, especially suboptimal levels, with sarcopenia risk.This genome-wide genetic association study was performed from August 2022 to February 2023 among the 295 489 unrelated European participants from the UK Biobank (2006-2010). Nonlinear and standard mendelian randomization analyses were used to examine the association of serum 25(OH)D concentration with sarcopenia risk.A weighted genetic risk score using 35 unrelated single-nucleotide variants from the UK Biobank and weights from the SUNLIGHT Consortium was selected as an instrumental variable for serum 25(OH)D concentration.The primary outcome was sarcopenia, and the secondary outcomes consisted of grip strength, appendicular lean mass index, and gait speed.The final genetic analyses included 295 489 participants (mean [SD] age, 56.3 [8.1] years; 139 216 female [52.9%]). There was an L-shaped association between genetically predicted serum 25(OH)D concentration and sarcopenia risk. The risk of sarcopenia decreased rapidly as 25(OH)D concentration increased until 20 ng/mL and then leveled off. The odds ratio of sarcopenia for serum 25(OH)D level of 10 vs 20 ng/mL was 1.74 (95% CI, 1.17-2.59). Similar patterns were also observed when the association between serum 25(OH)D concentration and risks of each of the sarcopenia indices were evaluated.In this mendelian randomization genetic association study of adults in the UK Biobank, the findings supported a nonlinear association between suboptimal 25(OH)D levels and sarcopenia risk. Randomized clinical trials among participants with suboptimal 25(OH)D levels are required to verify the potential causality.